1. Technical Field
This disclosure relates generally to methods and compositions for treating wounds. More particularly, wounds are treated with a biodegradable composition containing oxidized cross-linked dextran or dextran derivative having a charged induced thereon.
2. Background of Related Art
Dextran is a polysaccharide which is produced from sucrose by bacteria belonging to the genera Leuconostoc, Streptococcus and Lactobacillus, all of which belong to the family Lactobacillaceae. The majority of known dextrans are formed by strains of Leuconostoc mesenteroides. Dextran, in which 1-6 linkages predominate, may be represented as follows: ##STR1##
Dextran has been employed in the treatment of wounds. In particular, an insoluble hydrophilic cross-linked dextran polymer in powder form has been found to be especially useful for the debridement of wounds, i.e., the removal of foreign bodies, pus, exudates and irrevocably damaged and devitalized tissue from tissue wounds. This dextran polymer, which is formed by crosslinking dextran with epichlorohydrin, is applied to heavily exudating wounds, allowed to gel and then washed out. The crosslinked dextran, commercially known as DEBRISAN.RTM., absorbs the exudates, including the components that tend to impede tissue repair. Consequently, this composition promotes wound healing by retarding eschar formation and by keeping lesions soft and pliable.
Dextran which is crosslinked with epichlorohydrin is described in U.S. Pat. No. 3,042,667 and in British Patent No. 1,013,585 and commercially available under the tradename SEPHADEX from Pharmacia Corp., Piscataway, N.J. Epichlorohydrin (CH.sub.2 OCHCH.sub.2 Cl) reacts with the pendant hydroxyl groups on dextran to form ether bound bridges between dextran chains. These ether bonds are not susceptible to degradation at physiological pH. Thus, the resulting crosslinked dextran is not considered to be biodegradable, a factor which considerably limits the utility of such crosslinked dextran.
U.S. Pat. No. 4,963,666 describes a method for overcoming this deficiency by providing a crosslinked dextran material containing ester bound crosslinking bridges. Ester bonds are much more susceptible to hydrolytic degradation at physiological pH than are ether bonds. The method of obtaining these ester bonds involves reacting a carboxyl-containing polysaccharide, e.g., hyaluronic acid, pectin, xanthan, alginic acid or an anionic derivative of a neutral polysaccharide such as carboxymethyl dextran, with an epoxy-type activating reagent such as epichlorohydrin. The resulting crosslinked dextran forms a gel of controllable degradability which may be employed as a tissue anti-adhesion agent, a drug-release agent or a wound dressing. U.S. Pat. No. 4,591,638 discloses that dextran can be crosslinked via ester bonds by reacting dextran with reactive derivatives of dicarboxylic acids, e.g., diacyl halides.
Oxidation of polysaccharides including dextran has been performed for various purposes. For example, U.S. Pat. No. 2,988,455 describes water resistant cross-linked polysaccharide compositions wherein polysaccharide film-forming gums are cross-linked polysaccharide compositions wherein polysaccharide film-forming gums are cross-linked in combination with dialdehyde or periodate oxidized polysaccharides useful in forming films, coatings and innocuous vehicles for fillers.
U.S. Pat. No. 4,370,476 relates to the preparation of Ferric hydroxide complexes of dextran carboxylic acids. U.S. Pat. No. 4,339,360 relates to the production of particles of an activated oxidized polysaccharide substance (e.g., Sephadex) coated with an inactive protective layer. U.S. Pat. No. 4,308,254 relates to a porous solid material for use in a chromatography column prepared by a method which includes the step of oxidizing a support which may secondarily cross-linked DEAE dextran.